Seminar 302 2014
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Transcript of Seminar 302 2014
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Influenza A virus – From biology to vaccines
• Samita AndreanskyDepartments of Microbiology and
Immunology, Pediatrics and Medicine
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Influenza kills 20-30,000 Americans each year. About 40,00 die in road accidents
Young and Elderly are most vulnerable
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1918 Spanish Flu Approx 20-40 million deaths
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America’s deaths from influenza were greater than the number of U.S. servicemen killed in any war
Series10
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Civil WWI 1918-19 WWII Korean Vietnam War Influenza War War
Thousands
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• The influenza virus is a upper respiratory tract infection caused by one of the influenza virus pathogens (Type A, B, or C).
• Although it is called a respiratory disease, it affects the whole body, making you feel sick all over.
http://www.nlm.nih.gov/medlineplus/ency/imagepages/17237.htm
Where does Influenza virus acts on the body
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Virus – Host Interaction
Virus Attachment Protein: Hemagglutinin
Host receptor : Sialic Acid
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viralzone.expasy.org
Host receptor specificity
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• Tiny droplets that come from a person’s mouth and nose when they cough and sneeze.
• • Touching objects
contaminated with particles from an infected person’s nose and throat.
http://www.lungusa.org/diseases/c&f02/influenza.html#what
Transmission from person to person by:
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• Symptoms begin 1-4 days after infection. • You can spread the flu before your symptoms start and
3-4 days after your symptoms appear. • The following symptoms of the flu can vary depending
on the type of virus, a person’s age and overall health:– Sudden onset of chills and fever (101 – 103 degrees F)– Sore throat, dry cough – Fatigue, malaise – Terrible muscle aches, headaches– Diarrhea– Dizziness
Symptoms
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• A bacterial “superinfection” can develop when the influenza virus infects the lungs.
• The result? – The bacteria that live in the nose and throat can descend to the lungs
and cause bacterial pneumonia. • Who is most at risk?
– People over 50, infants, those with suppressed immune function or chronic diseases.
• Other complications include bronchitis, sinusitis and ear infections.
http://www.ecureme.com/atlas/version2001/atlas.asp
Complications of Flu
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Influenza A virus
• Nucleic acid : RNA
• Enveloped virus
• Viral family: Orthomyxoviridae
• Three types• A, B, C
Influenza viruses are small.Average eukaryotic cells is 10,000 nm in diameter (10 microns) 100 times bigger than the influenza virus diameter
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Different Species – Different Genes
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A/Fujian/411/2002 (H3N2)
NeuraminidaseHemagglutini
n
Type of nuclearmaterial
Virustype
Geographicorigin
Strainnumber
Year of isolation
HA and NA
substrain
Virus Nomenclature
Serotypes in humans
HA 1-16NA 1-9
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Drift and Shift generates new viruses
Evolutionary Survival Strategy for the virus
Host immune response : Clears the infection
Our Immune System is like an army
www.avaara.com
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•Gradual Change• Due to point mutations in HA and NA• Occurs in both A and B viruses
DRIFT
old neuraminidase new neuraminidase
Drift
http://www.biotech.ubc.ca/db/TEACH/BANK/
PPT/flu2.ppt
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•Eight-member Gene Teams” with each member being a separate Player•Promiscuity of the virus – they can give away genes and acquire new segments
Shift – Reassortment of genes
•Occurs through assortment of genes• Sudden change and cause for pandemics• Occurs only in influenza A viruses• We have no pre-existing immunity
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Deaths
20% were 10 years old or under
64% were 25 years old or under
87% were 35 years old or under
Median Age 16-20 years old
Avian H5N1 Virus jumped species
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2009 Swine H1N1 Flu “You have killed us all”
Death - 17,770 people in 213 countries in 2009
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1918 1957 1968 1977 19971998/9
2003
H1
H1H3
H2
H7H5H5
H9
SpanishInfluenza
AsianInfluenza
RussianInfluenza
AvianInfluenza
Hong KongInfluenza
Timeline of influenza infection
2014
Swine H1
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“The pandemic clock is ticking, we just don’t know what time it is”
E. Marcuse
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• Inactivated vaccine• (generates only antibody response)
• Live attenuated vaccine (generates both antibody and T cell responses)
Annual
Cornerstone of Prevention
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Immunology 101
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Host response to viral infection
• Antibodies against Hemagglutinin
• CD8 T cells lyse infected cells
• CD4 T cells
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surveillance
select strains
prepare reassortants
standardize antigen
assign potency
review/license
formulate/test/package
vaccinate
WHO/CDC)
WHO/CDC/FDA
CDC/FDA
FDA
FDA
FDA
manufacturers
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
clinic
Vaccine Production
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Cell SubstratePreparation
Remove Cells,Purify Virus
Infect &Incubate
InactivateVirus
Influenza Vaccine Production
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• Selection of strains difficult and time consuming
• Annual, seasonal production
• Technical process, specialized facilities
• Lack of cross protection against antigenic variants Long term protection uncertain ??
• Relatively high cost
• Annual vaccine administration is required26
Constraints of Vaccine Production
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Pre-pandemic: Vaccine Planning
• Definition: Vaccines developed against influenza viruses that are currently circulating in animals and that have the potential to cause a pandemic in humans
• Rationale: might provide priming or “limited protection” against pandemic strain Goal: Reduce morbidity or mortality Might not reduce number of viral infections
• Problem: Which vaccine strains, and when should it be given?
27
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Despite . . . – Expanded global and national surveillance – Better healthcare, medicines, diagnostics– Greater vaccine manufacturing capacity
New risks:– Increased global travel and commerce– Greater population density– More elderly and immunosuppressed– More daycare and nursing homes– Bioterrorism
Pandemic Flu Today
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